This continuation application is to provide advanced training to predoctoral and postdoctoral fellows in the fundamentals of neuronal plasticity in the aging nervous system. The program has three key features: 1) Academic bridging - A principal focus will be to provide the students and fellows with concepts and research experience that address problems at the interface of basic and clinical problems in aging. This bridging will be reflected in the faculty participating in the program, the trainees admitted to the program, and the structure of the training program itself. Courses, seminars, annual scientific retreat, and co-sponsorships by basic scientists and clinical researchers of trainees will bring together these bridging concepts and research practice. 2) Life span development - We believe that the aging process is part of a life span process, which should and can be investigated as part of a continuum from birth to death. Many conceptual and practical problems presently being addressed in early development are translatable to late stage aging. This translation of ideas and approaches from studies of development and adult plasticity will be a feature of the program. We believe that investigations of neuronal plasticity are at the very core of understanding late stage aging of the nervous system, since age-related decline often reflects a decrease in neuronal and functional plasticity. In this program, we will encourage the participants to address these age-related aspects of plasticity, disease, and neurodegeneration. 3) Multi-disciplinary - By its very nature, Neuroscience and Aging are multi-disciplinary fields of investigation. The modern neuroscientist is required to understand and use methods and techniques from the full range of biological disciplines and beyond. The faculty in this program (46 at current time) represents technical expertise in the fields of Molecular Genetics, Protein Chemistry, Cell Biology, Neurophysiology, Systems Analysis, Pharmacology, Cognitive Neuroscience, Computational Neuroscience, and Clinical Neurology. The students (six per year at second year of training and beyond) are drawn from the Neurosciences Graduate Program, a highly regarded program with strong participation from UCSD and the neighboring institutions, including Salk, Scripps, and Sanford-Burnham Institutes. Postdoctoral trainees (six per year) are drawn from the laboratories of the same participating faculty members. Our goal is to train students and fellows to be able to work and think effectively in several of these areas and will be achieved by providing them a forum for instruction, discussion, and interaction; in so doing, they represent the next generation of neuroscientists who will contribute to the advancement in aging research.